The present invention relates to novel pyrazole derivatives and a therapeutic agent for diabetes containing such compounds as the active ingredient.
Na+-dependent glucose transporter (SGLT) is a membrane protein which transports glucose, and SGLT-1 and SGLT-2 are known. In the renal uriniferous tubules, the SGLT-2 is mainly expressed. Glucose that is filtered in glomeruli is reabsorbed at the renal uriferous tubules via SGLT, and the glucose taken is reused in the body through the bloodstream. When the SGLT-2 is inhibited, the amount of glucose reabsorbed at renal uriniferous tubles lowers, and the glucose is excreted in urine. As a result, it is considered that the level of blood glucose decreases. Therefore, it is considered that an SGLT inhibitor which is effective when administered orally is useful for treating diabetes.
There is known 3-(benzo[b]furan-5-yl)-2′,6′-dihydroxy-4′-methylpropiophenone 2′-O-(6-O-methoxycarbonyl-β-D-glucopyranoside) as a compound that can inhibit the SGLT and promote the action of urinary sugar excretion in the animals (J. Med. Chem., 42, 5311-5324, 1999). Oral administration of the above-mentioned compound to the rat indicates the increase in the amount of sugar excreted in urine and the decrease in the level of blood sugar (Diabetes, Vol. 48, pp. 1794-1800, 1999). However, there is the shortcoming that the dose needed to exhibit the efficacy is as large as 100 mg/kg. Further, the evaluation system by a glucose tolerance test shows that compounds disclosed in WO 0116147 are effective at a dose of 10 mg/kg in the rats by intravenous administration or subcutaneous administration. However, there is no description about the efficacy of those compounds by oral administration.